A Comparison between Recombinant Activated Factor VII (Aryoseven) and Novoseven in Patients with Congenital Factor VII Deficiency

In order to establish the efficacy and biosimilar nature of AryoSeven to NovoSeven in the treatment of congenital factor VII (FVII) deficiency, patients received either agent at 30 1/4g/kg, intravenously per week for 4 weeks, in a randomized fashion. The primary aim was to compare FVII:coagulation activity (FVII:C), 20 minutes after recombinant activated FVII (rFVIIa) injection, in the 2 groups. A secondary measure was self-reported bleeding. The median interquartile baseline range of the plasma level of activated FVII (FVIIa) activity in the 2 groups was 1.6 (1.1-14.0) IU/dL and 5.0 (1.1-25.5) IU/dL. All patients achieved levels of FVIIa (FVII:C) >30 IU/dL, 20 minutes after the injection of rFVIIa. Bleeding was similar between the 2 groups, with a comparable decrease in severity and frequency compared to the last month prior to treatment. AryoSeven is similar to NovoSeven in increasing postinjection FVIIa activity as well as in clinical safety and efficacy. © The Author(s) 2014

A double-blind, randomized comparison study between Zytux� vs MabThera® in treatment of CLL with FCR regimen: Non-inferiority clinical trial

Background: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to CLL chemotherapy regimens has been associated with improved survival. The aim of this study was to establish efficacy and safety of Zytux� in comparison to MabThera® in treatment of CLL. Materials and Methods: Seventy CLL patients who met the criteria for entering the study were randomized into two groups (35 patients in each group). Both groups received Fludarabine and Cyclophosphamide plus Rituximab as part of the FCR regimen. Group A was treated with Zytux�, and group B was treated with MabThera®. A non-inferiority margin of 20 for the primary outcome was defined to examine the similarity between Zytux� and MabThera®. Results: Baseline demographic characteristics showed no statistically significant difference between the two groups. The two treatment groups were comparable in terms of laboratory and clinical findings, cellular index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the end of the treatment period. Regarding safety results, Zytux� demonstrated a similar profile of adverse reactions in comparison to MabThera®. Moreover, the overall response rate was 88 and 89 for Zytux� and MabThera®, respectively (CI -0.17, 0.18). Conclusion: Results showed non-inferiority of Zytux� in terms of efficacy and adverse events as a biosimilar version of MabThera®. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

A double-blind, randomized comparison study between Zytux� vs MabThera® in treatment of CLL with FCR regimen: Non-inferiority clinical trial

Background: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to CLL chemotherapy regimens has been associated with improved survival. The aim of this study was to establish efficacy and safety of Zytux� in comparison to MabThera® in treatment of CLL. Materials and Methods: Seventy CLL patients who met the criteria for entering the study were randomized into two groups (35 patients in each group). Both groups received Fludarabine and Cyclophosphamide plus Rituximab as part of the FCR regimen. Group A was treated with Zytux�, and group B was treated with MabThera®. A non-inferiority margin of 20 for the primary outcome was defined to examine the similarity between Zytux� and MabThera®. Results: Baseline demographic characteristics showed no statistically significant difference between the two groups. The two treatment groups were comparable in terms of laboratory and clinical findings, cellular index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the end of the treatment period. Regarding safety results, Zytux� demonstrated a similar profile of adverse reactions in comparison to MabThera®. Moreover, the overall response rate was 88 and 89 for Zytux� and MabThera®, respectively (CI -0.17, 0.18). Conclusion: Results showed non-inferiority of Zytux� in terms of efficacy and adverse events as a biosimilar version of MabThera®. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency

Background: Human fibrinogen concentrate (HFC) corrects fibrinogen deficiency in congenital a-/hypofibrinogenemia. Objectives: To assess pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF), and safety of a new double virusinactivated/eliminated, highly purified HFC vs. active control. Patients/Methods: In this multinational, randomized, phase II, open-label, crossover study in 22 congenital afibrinogenemia patients aged >= 12 years, 70 mg kg(-1) of new HFC (FIBRYGA, Octapharma AG) or control (Haemocomplettan (R) P/RiaSTAP (TM), CSL Behring GmbH) were administered, followed by crossover to the other concentrate. Fibrinogen activity, PK and MCF in plasma were assessed. Results: The concentrates were not bioequivalent for the primary endpoint, AUC(norm) (mean ratio, 1.196; 90% confidence interval [CI], 1.117, 1.281). Remaining PK parameters (C-maxnorm, IVR, t(1/2), MRT) reflected bioequivalence between concentrates, except for clearance (mean ratio, 0.836; 90% CI, 0.781, 0.895) and V-ss (mean ratio, 0.886; 90% CI, 0.791, 0.994). Mean AUC(norm) was significantly larger for the new HFC (1.62 +/- 0.45 vs. 1.38 +/- 0.47 h kg g L-1 mg(-1), P = 0.0001) and mean clearance was significantly slower (0.665 +/- 0.197 vs. 0.804 +/- 0.255 mL h(-1) kg(-1), P = 0.0002). Mean MCF increased from 0 mm to 9.68 mm (new HFC) and 10.00 mm (control) 1-hour post-infusion (mean difference, -0.32 mm; 95% CI, -1.70, 1.07, n.s.). No deaths, thromboses, viral seroconversions or serious related adverse events occurred. Conclusions: Bioequivalence was not demonstrated for AUC(norm), clearance and V-ss. Larger AUC(norm) and slower clearance were observed for the new HFC. Remaining pharmacokinetic parameters reflected bioequivalence to control. Safety profiles and increases in clot strength were comparable between concentrates

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study

Background Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. Objective To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. Methods European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. Results Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII:C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). Conclusions An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.Peer reviewe

Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease : Results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Background Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. Results In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels <20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.Peer reviewe

Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disease characterized by prolonged bleeding time with normal platelet count and morphology. It is caused by the quantitative or qualitative deficiency of the platelet glycoprotein IIb-IIIa. In 382 Iranian patients with GT diagnosed at a single center during the period 1969-2001, consanguinity between parents was 86.6%, in accord with the high frequency of intrafamilial marriages in Iran. Almost all patients had had abnormal mucocutaneous bleeding (epistaxis and gum bleeding); at follow-up, 4/5 of the patients had been transfused at least once to control hemorrhagic episodes. As expected, almost all the patients had a normal platelet count while the leukocyte count was increased in 19.3%. Among women, an unexpected low rate of pregnancies was observed

MIXED HYALINE VASCULAR AND PLASMA CELL TYPE CASTLEMAN’S DISEASE: REPORT OF A CASE

Castleman’s disease (angiofollicular lymphoid hyperplasia) includes a heterogeneous group of lymphoproliferative disorders. The cause of this disease remains uncertain. There are two types of localized Castleman’s disease: the more common hyaline vascular and the plasma cell types. Mixed variant is an uncommon localized lesion in general population. The lesions can occur in any part of the body that contains lymphoid tissue, although seventy percent are found in the anterior mediastinum. We report a thirty years old boy with Castleman’s disease who presented with fever, anorexia, weight loss,sweating, anemia and abdominal mass. The histologic examination of the biopsy specimens revealed a mixed hyaline vascular and plasma cell type of Castleman’s disease

Polymorphism in the DNA repair gene XRCC3 and therapeutic outcomes in patients with AML

Among the lesions induced by chemotherapeutic drugs, DNA double-strand breaks (DSB) are considered the most serious ones that can result in cell death, if it is not properly repaired. Homologous recombination (HR) pathway is the main system for DSB repair and XRCC3 has a key role in this pathway. Protein activity can be affected by the XRCC3 polymorphism. Thus, in this study, the association between XRCC3 Thr241Met polymorphism and therapeutic outcomes was investigated. The study population consisted of 67 adult patients with de novo AML(range: 15-65 years). XRCC3 Thr241Met polymorphism was determined by PCR-RFLP technique. Clinical data were collected from patients� medical records. There were no significant association between XRCC3 genotype and therapeutic outcome (P=0.764). We found no considerable correlation between XRCC3 genotype and age (P=0.255), gender (P=0.239), AML-subtype (P=0.961) as well asWBC count (P=0.629). There are only a few studies conducted on the relationship between therapeutic outcomes and XRCC3 Thr241Met polymorphism in AML patients and the reported findings are controversial. Accordingly, further studies will be required to clarify the effect of XRCC3 Thr241Met polymorphism on therapeutic outcome. © 2015, Iranian Neurogenetics Society. All rights reserved

The Comparison Of The Efficacy Of Cefriaxon Monotherapy With Ceftazidim Plus Amikacin As Initial Empiric Antibiotic Therapy In Febrile Neutropenic Patients Emam Hospital (2000-2001)

Neutropenic state with fever is exactly regarded as a medical emergency, with high mortality and morbidity rate, unless treated urgently and correctly. Every attempt should be made to find and establish the offending organism, but postponing treatment until obtaining culture results is not advised. Controversy exist on which antibiotic regimen to be used while waiting for culture results. Many antibiotic regiments both monotherapy or combination treatments have been used with varying result. The objective of this study is to compare the efficacy of cefriaxon monothenapy with ceftazidim. Plus Amikacin as initial empiric antibiotic therapy in febrile neutropenic patients.&quot;nMaterials and Methods: We performed a randomized, single blind clinical trial in 57 adult (age&amp;gt;12 years), neutropenic (PMN&amp;lt;1000) patients with fever (Temperature, oral &amp;gt;38.5c) in Hematology ward, Imam khomeini hospital. After careful physical exam and obtaining blood &amp;amp; urine samples for culture, the patients were randomized to each of the two arms: Cefriaxon 2 grams daily, intravenously (arm A) and; Ceftazidim 2g thrice daily plus amikacin 500 mg twice daily (arm B). Patients with shock, organ failure or previous antibiotic intake (during 48 hour before fever) were excluded. If needed, dose adjustment of drugs were allowed. Effervescence in 3 days following initiation of treatment, lasting 48 hours or more, were regarded as effective (positive result).&quot;nResults: During a twelve months period of study, a total of 57 patients (17female, 40male) were included. They were randomly selected to each arm of empirical treatment. Of 28 pts in arm A, 19 (67 percent), the treatment was effective, compared to 15 of 29 (51.7 percent) in groups B. The duration of fever after initiation of treatment was 37.9 &amp;plusmn; 17 hours in arm A and 40. 1 &amp;plusmn; 20 h in arm B. Blood and / or urine culture was equally positive in two arms (25 percent in arm A and 27.6 percent in arm B).&quot;nConclusion: Cefriaxon monotherapy is at least equally effective in low risk neutropenic patients with fever compared to combination of ceftazidim plus amikacin at a decreased cost and probably (expected) less adverse side effects in our patients.&quot;n&amp;nbsp